PARP inhibitors suppress tumours via centrosome error-induced senescence independent of DNA damage response.

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as promising chemotherapeutic drugs primarily against BRCA1/2-associated tumours, known as synthetic lethality. However, recent clinical trials reported patients' survival benefits from PARP inhibitor treatments, irrelevant to homologous recombination deficiency. Therefore, revealing the therapeutic mechanism of PARP inhibitors beyond DNA damage repair is urgently needed, which can facilitate precision medicine. METHODS: A CRISPR-based knock-in technology was used to establish stable BRCA1 mutant cancer cells. The effects of PARP inhibitors on BRCA1 mutant cancer cells were evaluated by biochemical and cell biological experiments. Finally, we validated its in vivo effects in xenograft and patient-derived xenograft (PDX) tumour mice. FINDINGS: In this study, we uncovered that the majority of clinical BRCA1 mutations in breast cancers were in and near the middle of the gene, rather than in essential regions for DNA damage repair. Representative mutations such as R1085I and E1222Q caused transient extra spindle poles during mitosis in cancer cells. PAR, which is synthesized by PARP2 but not PARP1 at mitotic centrosomes, clustered these transient extra poles, independent of DNA damage response. Common PARP inhibitors could effectively suppress PARP2-synthesized PAR and induce cell senescence by abrogating the correction of mitotic extra-pole error. INTERPRETATION: Our findings uncover an alternative mechanism by which PARP inhibitors efficiently suppress tumours, thereby pointing to a potential new therapeutic strategy for centrosome error-related tumours. FUNDING: Funded by National Natural Science Foundation of China (NSFC) (T2225006, 82272948, 82103106), Beijing Municipal Natural Science Foundation (Key program Z220011), and the National Clinical Key Specialty Construction Program, P. R. China (2023).

Fertility history and intentions of married women, China.

Objective: To estimate the proportion of married women in China who intend to become pregnant given the country's pronatalist population policy and to investigate fecundity, with an emphasis on the influence of socioeconomic factors. Methods: A nationally representative survey of 12 815 married women aged 20 to 49 years (mean: 36.8 years) was conducted during 2019 and 2020. All completed questionnaires, 10 115 gave blood samples and 11 710 underwent pelvic ultrasound examination. Fertility intention was the desire or intent to become pregnant combined with engagement in unprotected sexual intercourse. We defined infertility as the failure to achieve pregnancy after 12 months or more of unprotected intercourse. We considered an anti-Müllerian hormone level < 1.1 ng/mL and an antral follicular count < 7 as indicating an abnormal ovarian reserve. Findings: Fertility intentions were reported by 11.9% of women overall but by only 6.1% of current mothers (weighted percentages). Fertility intention was significantly less likely among women in metropolises (odds ratio, OR: 0.38; 95% confidence interval, CI: 0.31-0.45) and those with a higher educational level (OR: 0.74; 95% CI: 0.62-0.88). Overall, 18.0% had experienced infertility at any time and almost 30% had an abnormal ovarian reserve on assessment. An abnormal ovarian reserve and infertility were less likely in women in metropolises (P < 0.05) but more likely in obese women (P < 0.05). Conclusion: The willingness of Chinese married women to give birth remained low, even with relaxation of the one-child policy.

Risk Factors of the Occurrence and Treatment Failure of Refractory Peritoneal Dialysis-Associated Peritonitis: A Single-Center Retrospective Study From China.

BACKGROUND: This study aimed to investigate the clinical characteristics and prognosis of refractory peritoneal dialysis (PD)-associated peritonitis as well as the risk factors of its occurrence and treatment failure. METHODS: A single-center retrospective cohort study was conducted among 519 patients undergoing PD from January 2007 to October 2021. According to the International Society for Peritoneal Dialysis guidelines, all episodes occurred in our center were divided into two groups: refractory and nonrefractory. Demographic, biochemical, and pathogenic bacteria and treatment outcome data were collected. RESULTS: During the 15-year period, 282 episodes of peritonitis occurred in 166 patients undergoing PD. The refractory rate was 34.0% (96/282). Gram-positive organisms were the leading cause of peritonitis (47.9%); however, gram-negative organisms were predominant in refractory peritonitis (34.4%, p = 0.002). Multiple logistic regression revealed that gram-negative organism-based peritonitis, longer PD duration, and female sex were the significant independent predictors of refractory peritonitis. Among 96 refractory episodes, white blood cell (WBC) count, dialysate WBC on Day 3, and PD duration ≥5 years were the independent risk factors of treatment failure. CONCLUSIONS: Gram-negative organism-based peritonitis, longer PD duration, and female sex were the independent risk factors of refractory peritonitis. Refractory peritonitis with higher WBC count, higher dialysate WBC on Day 3, and PD duration ≥5 years increased treatment failure risk and required immediate PD catheter removal. The timely identification of refractory peritonitis with high risk of treatment failure as well as timely PD catheter removal is important.

Impacts of male chromosomal polymorphisms on semen quality and IVF/ICSI outcomes: A retrospective cohort study.

OBJECTIVE: The study aims to elucidate the impacts of different types of male chromosomal polymorphisms (MCPs) on various outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment. METHODS: This retrospective cohort study included 1442 couples with normal karyotypes, 1442 couples with MCPs, 42 couples with male chromosomal rearrangements (MCRs), and 42 couples with MCRs combined with MCPs who underwent IVF/ICSI treatment at Peking University Third Hospital from 2015 to 2021. The semen quality, embryological outcomes, and clinical outcomes of different groups stratified by karyotypes were compared. RESULTS: For couples undergoing IVF, male inv(9) was associated with a significantly lower sperm viability rate (29.41% vs 34.49%, P = 0.030), a lower progressive motility rate (25.13% vs 30.50%, P = 0.013), and a lower normal fertilization rate (52.41% vs 59.84%, P = 0.014). Male 9qh + was related to a lower sperm viability rate (27.56% vs 34.49%, P = 0.028). No MCPs were observed to compromise clinical outcomes in couples undergoing IVF. For couples undergoing ICSI, no MCPs exhibited an association with poorer semen quality and embryological outcomes. However, Yqh + and DGpstk+ were found to be significantly correlated with an increased likelihood of preterm birth (23.3% vs 9.2%, P = 0.003; 20.0% vs 9.2%, P = 0.041, respectively). In couples with MCRs, the presence of MCPs significantly reduced the sperm viability rate (19.99% vs 30.97%, P = 0.017) and progressive motility rate (8.07% vs 27.85%, P = 0.018). CONCLUSION: Our study provides detailed evidence for the impacts of various MCPs on IVF/ICSI outcomes, reveals the complexity and heterogeneity of these impacts, and highlights the adverse effects of male inv(9).

Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles.

BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

Efficacy and safety of mesenchymal stem cell therapy for ovarian ageing in a mouse model.

BACKGROUND: Ovarian ageing is one of the major issues that impacts female fertility. Mesenchymal stem cell (MSC)-based therapy has made impressive progress in recent years. However, the efficacy and safety of MSCs, as nonautologous components, remain to be further verified. METHODS: Two common sources of MSCs, umbilical cord-derived MSCs (UC-MSCs) and adipose tissue-derived MSCs (AD-MSCs), were orthotopically transplanted into a mouse model of ovarian ageing to evaluate their therapeutic effects. The safety of the treatment was further evaluated, and RNA sequencing was performed to explore the underlying mechanisms involved. RESULTS: After orthotopic transplantation of MSCs into the ovary, the oestrous cycle, ovarian weight, number and proportion of primary follicles, granulosa cell proliferation, and angiogenesis were improved. The effects of AD-MSCs were superior to those of UC-MSCs in several indices, such as post-transplant granulosa cell proliferation, ovarian weight and angiogenesis. Moreover, the tumorigenesis, acute toxicity, immunogenicity and biodistribution of MSCs were evaluated, and both AD-MSCs and UC-MSCs were found to possess high safety profiles. Through RNA sequencing analysis, enhancement of the MAPK cascade was observed, and long-term effects were mainly linked to the activation of immune function. CONCLUSIONS: Orthotopic transplantation of MSCs displays significant efficacy and high safety for the treatment of ovarian ageing in mice.

Gut symbionts alleviate MASH through a secondary bile acid biosynthetic pathway.

The gut microbiota has been found to play an important role in the progression of metabolic dysfunction-associated steatohepatitis (MASH), but the mechanisms have not been established. Here, by developing a click-chemistry-based enrichment strategy, we identified several microbial-derived bile acids, including the previously uncharacterized 3-succinylated cholic acid (3-sucCA), which is negatively correlated with liver damage in patients with liver-tissue-biopsy-proven metabolic dysfunction-associated fatty liver disease (MAFLD). By screening human bacterial isolates, we identified Bacteroides uniformis strains as effective producers of 3-sucCA both in vitro and in vivo. By activity-based protein purification and identification, we identified an enzyme annotated as ß-lactamase in B. uniformis responsible for 3-sucCA biosynthesis. Furthermore, we found that 3-sucCA is a lumen-restricted metabolite and alleviates MASH by promoting the growth of Akkermansia muciniphila. Together, our data offer new insights into the gut microbiota-liver axis that may be leveraged to augment the management of MASH.

Exposure to heavy metallic and trace essential elements and risk of diminished ovarian reserve in reproductive age women: A case-control study.

The associations between metallic elements and ovarian reserve function have remained uncertain yet. In this case-control study, we involved 149 women with diminished ovarian reserve (DOR) and 151 women with normal ovarian reserve, and assessed the levels of six heavy metallic (Cr, Cd, As, Hg, Pb, and Mn) and seven trace essential (Se, Fe, Zn, Co, Mo, Cu, I) elements in their follicular fluid with inductively coupled plasma mass spectrometry. Associations were examined with logistic regressions and Bayesian kernel machine regression (BKMR). As a result, we found that the medium and the highest tertiles of Pb were significantly associated with an increased likelihood of DOR compared to the lowest tertile, while the medium or/an the highest tertiles of Cu, I, and Fe showed significantly lower likelihoods of DOR compared to the lowest tertiles. Cu and Pb showed significantly non-linear associations with ovarian reserve markers such as follicle-stimulating, anti-mullerian hormone levels, and antral follicle count. With the rising overall concentrations of heavy metals, the likelihood of DOR increased although not significant. There was a trend of a "U-shaped" association across the whole concentration range of trace essential elements and the likelihood of DOR. Our study revealed that avoiding heavy metallic elements and properly supplementing trace essential elements are conducive to ovarian function.

Intracytoplasmic sperm injection versus in vitro fertilization in infertile women with thyroid autoimmunity.

BACKGROUND: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared to in vitro fertilization (IVF). METHODS: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer treatment cycle from January, 2019 to February, 2021. In total, 2,171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8,702 and 2,688 women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy and live birth after the first embryo transfer cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. RESULTS: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in TAI-positive and IVF group vs. 0.7 [0.5-0.8] in TAI-positive and ICSI group vs. 0.6 [0.5-0.8] in TAI-negative and IVF group vs. 0.7 [0.5-0.8] in TAI-positive and ICSI group, p<0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio: 0.80, 95% CI: 0.67-0.97); clinical pregnancy: 43.0% vs. 38.8%, adjusted odds ratio: 0.81, 95% confidence interval [CI]: 0.67-0.97; live birth: 36.2% vs. 32.4%, adjusted odds ratio: 0.81, 95% CI: 0.66-0.98). CONCLUSION: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared to IVF. Further prospective clinical trials are needed to confirm our findings.

Ultrafast-laser-inscribed multiscan type-I mid-infrared waveguides and beamsplitters in IG2.

This study reports the fabrication and characterization of various configurations of mid-infrared waveguides and beamsplitters within the chalcogenide glass IG2 using ultrafast laser inscription (ULI). Our investigation reveals two distinct regimes of ULI modification: weak and strong. The strong regime, marked by higher pulse energies, presents darker and prominent waveguide morphology, enabling efficient light guiding at 4.55 µm, but with higher scattering losses at shorter wavelengths. In the weak regime, we observed a significant enhancement in the mode confinement and a reduction in the propagation loss within the multilayer structures. We have investigated key geometric and inscription parameters such as inscription pulse energy and number of layers, as well as arm separation and splitting angles for beamsplitters. We have successfully fabricated beamsplitters with configurations ranging from 1 × 2 to 1 × 8, achieving a uniform splitting ratio over 96% and a splitting loss as low as 0.4 dB at 4.55 µm. These findings highlight the significant potential of ULI-based IG2 waveguides and beamsplitters for mid-infrared photonics.

Effects of hysteroscopic septum incision versus expectant management on IVF outcomes in women with complete septate uterus: a retrospective study.

OBJECTIVE: This retrospective study aimed to assess the impact of hysteroscopic septum incision on in vitro fertilization (IVF) outcomes among infertile women diagnosed with a complete septate uterus and no history of recurrent pregnancy loss. METHODS: The study was conducted at a tertiary reproductive center affiliated with a university hospital and involved 78 women with a complete septate uterus. Among them, 34 women underwent hysteroscopic septum incision, while 44 women opted for expectant management. The primary outcome measure was the live birth rate, while secondary outcomes included clinical pregnancy rate, preterm birth rate, miscarriage rate, and ongoing pregnancy rate. RESULTS: Women who underwent hysteroscopic septum incision demonstrated a comparable likelihood of achieving a live birth compared to those managed expectantly (25% vs. 25%, Relative Risk (RR): 1.000, 95% Confidence Interval (CI): 0.822 to 1.216). No preterm births occurred in either group. The clinical pregnancy rate, ongoing pregnancy rate, and miscarriage rate showed no significant differences between the surgical group and the expectant management group. Subgroup analyses based on the type of embryo transferred also revealed no significant differences in outcomes. CONCLUSIONS: Hysteroscopic septum incision does not appear to yield improved IVF outcomes compared to expectant management in infertile women with a complete septate uterus and no history of recurrent pregnancy loss.

Optical structuring and finishing toward mid-spatial-frequency error reduction using femtosecond lasers.

We demonstrate nano-structuring and the reduction of mid-spatial-frequency errors using femtosecond laser figuring and finishing. For the first time, to the best of our knowledge, we have corrected mid-spatial-frequency errors from 17 nm to one nanometer in magnitude. We established a method for creating and predicting periodic nanostructures. This demonstration opens the path of using femtosecond lasers to correct surface errors that inherently result from sub-aperture manufacturing techniques.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

Testing Conditional Independence Between Latent Variables by Independence Residuals.

Conditional independence (CI) testing is an important problem, especially in causal discovery. Most testing methods assume that all variables are fully observable and then test the CI among the observed data. Such an assumption is often untenable beyond applications dealing with, e.g., psychological analysis about the mental health status and medical diagnosing (researchers need to consider the existence of latent variables in these scenarios); and typically adopted latent CI test schemes mainly suffer from robust or efficient issues. Accordingly, this article investigates the problem of testing CI between latent variables. To this end, we offer an auxiliary regression-based CI (AReCI) test by taking the measured variable as the surrogate variable of the latent variables to conduct the regression over the latent variables under the linear causal models, in which each latent variable has some certain measured variables. Specifically, given a pair of latent variables LX and LY , and a corresponding latent variable set LO , [Formula: see text] holds if and only if [Formula: see text] and [Formula: see text] are statistically independent, where A' and A'' are the two disjoint subset of the measured variable for the corresponding latent variables, A'{LO} ∩A''{LO} = ∅ , and ω1 is a parameter vector characterized from the cross covariance between A{LX} and A'{LO} , and ω2 is a parameter vector characterized from the cross covariance between A{LY} and A''{LO} . We theoretically show that the AReCI test is capable of addressing both Gaussian and non-Gaussian data. In addition, we find that the well-known partial correlation test can be seen as a special case of the AReCI test. Finally, we devise a causal discovery method by using the AReCI test as the CI test. The experimental results on synthetic and real-world data illustrate the effectiveness of our method.

Difference analysis and characteristics of incompatibility group plasmid replicons in gram-negative bacteria with different antimicrobial phenotypes in Henan, China.

BACKGROUND: Multi-drug-resistant organisms (MDROs) in gram-negative bacteria have caused a global epidemic, especially the bacterial resistance to carbapenem agents. Plasmid is the common vehicle for carrying antimicrobial resistance genes (ARGs), and the transmission of plasmids is also one of the important reasons for the emergence of MDROs. Different incompatibility group plasmid replicons are highly correlated with the acquisition, dissemination, and evolution of resistance genes. Based on this, the study aims to identify relevant characteristics of various plasmids and provide a theoretical foundation for clinical anti-infection treatment. METHODS: 330 gram-negative strains with different antimicrobial phenotypes from a tertiary hospital in Henan Province were included in this study to clarify the difference in incompatibility group plasmid replicons. Additionally, we combined the information from the PLSDB database to elaborate on the potential association between different plasmid replicons and ARGs. The VITEK mass spectrometer was used for species identification, and the VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). PCR-based replicon typing (PBRT) detected the plasmid profiles, and thirty-three different plasmid replicons were determined. All the carbapenem-resistant organisms (CROs) were tested for the carbapenemase genes. RESULTS: 21 plasmid replicon types were detected in this experiment, with the highest prevalence of IncFII, IncFIB, IncR, and IncFIA. Notably, the detection rate of IncX3 plasmids in CROs is higher, which is different in strains with other antimicrobial phenotypes. The number of plasmid replicons they carried increased with the strain resistance increase. Enterobacterales took a higher number of plasmid replicons than other gram-negative bacteria. The same strain tends to have more than one plasmid replicon type. IncF-type plasmids tend to be associated with MDROs. Combined with PLSDB database analysis, IncFII and IncX3 are critical platforms for taking blaKPC-2 and blaNDM. CONCLUSIONS: MDROs tend to carry more complex plasmid replicons compared with non-MDROs. The plasmid replicons that are predominantly prevalent and associated with ARGs differ in various species. The wide distribution of IncF-type plasmids and their close association with MDROs should deserve our attention. Further investigation into the critical role of plasmids in the carriage, evolution, and transmission of ARGs is needed.

A comparison of pregnancy outcomes and congenital malformations in offspring between patients undergoing intracytoplasmic sperm injection and conventional in vitro fertilization: a retrospective cohort study.

OBJECTIVE: To explore whether intracytoplasmic sperm injection (ICSI) would increase the malformation risk in fetuses and live births compared with conventional in vitro fertilization (IVF). DESIGN: Retrospective cohort study. PATIENT(S): Data were collected from couples who underwent conventional IVF or ICSI from January 2009 to December 2019 at the Center for Reproductive Medicine of Peking University Third Hospital in the People's Republic of China. A total of 46,167 conventional IVF fresh transfer cycles and 33,247 ICSI fresh transfer cycles were included. INTERVENTION(S): Intracytoplasmic sperm injection and conventional IVF. MAIN OUTCOME MEASURE(S): The primary outcomes were congenital abnormalities in live births. The secondary outcomes included the pregnancy outcomes, the malformations among the miscarriages, specific types of malformations in live births, birth weight, and sex. RESULT(S): The rates of congenital malformations in conventional IVF and ICSI were 5.44‰ and 5.78‰, respectively. There was no statistically significant difference between the two groups, as indicated by the adjusted odds ratio of 1.098 (95% confidence interval 0.787, 1.532). The rates of specific malformations were comparable between ICSI and IVF. Additionally, no discernible disparities were noted in pregnancy outcomes, the malformations among the miscarriages,birth weight between the two groups. CONCLUSION: Our study suggested the safety of ICSI and provided novel evidence by comparing pregnancy outcomes and congenital malformations in offspring between patients undergoing conventional IVF and ICSI.

[Genetic analysis of a case with mosaicism complex structural aberration of chromosome 18].

OBJECTIVE: To determine the karyotype of a patient with mosaicism complex structural aberration of chromosome 18. METHODS: A male patient with a 2-year history of infertility presented at the Center of Reproductive Medicine of the Third Hospital of Peking University in October 2019 was selected as the study subject. Clinical data of the patient was collected. Peripheral blood sample was taken for chromosomal karyotyping, copy number variation (CNV) analysis and fluorescence in situ hybridization (FISH) assay. Semen sample was taken for single sperm CNV analysis. RESULTS: The patient was found to have a karyotype of mos 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1].ish 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1]del(18)(q21q23)(D18Z1+,18p+,18q+,WCP18+),r(18)(q21q23)(WCP18+),r(18)(q21q23×2)(WCP18+). No pathogenic CNV was identified. Sequencing of 20 single sperms showed that 1 sperm was normal, 1 had yielded no result, 9 had harbored del(18q), 7 had harbored dup(18q)×2, and 2 had harbored dup(18q)×3. The dup/del fragments had both spanned approximately 33 Mb. CONCLUSION: It is rare for carriers of complex structural and numerical abnormalities of chromosome 18 to have a normal phenotype. Based on the accurate cytogenetic and molecular analyses and the single sperm CNV analysis, the influence of the aberrant karyotype on the gametogenesis may be evaluated.

Reproductive Outcomes of Conventional In Vitro Fertilization and Intracytoplasmic Sperm Injection in Patients with Non-Severe Male Infertility Across Poor and Different Sub-Optimal Ovarian Response Categories: A Cohort Study Based on 30,352 Fresh Cycles from 2009-2019.

Due to the influence of economic, social and many other factors, there are more and more reproductive problems. Originally introduced for managing male factor infertility, intracytoplasmic sperm injection had become the most commonly used fertilization treatment in the world, with broadened indications including low oocyte yield, prior fertilization failure with conventional in vitro fertilization etc. However, academic evidence for better live-birth outcomes of intracytoplasmic sperm injection over conventional in vitro fertilization is limited. Thus, we aimed to compare the reproductive outcomes of conventional in vitro fertilization and intracytoplasmic sperm injection in patients with non-severe male factor infertility across poor and different sub-optimal ovarian response categories. The fertility rate, implantation rate, clinical pregnancy rate, live birth rate and other obstetric outcomes were mainly compared. Our results showed that independent of the number of oocytes retrieved, intracytoplasmic sperm injection significantly increased the fertilization rate, while conventional in vitro fertilization cycles showed a higher implantation rate, clinical pregnancy rate, and live birth rate. No differences were observed in most obstetric outcomes. Our study indicates that poor ovarian response is not an indication for intracytoplasmic sperm injection in couples with non-severe male infertility.

Impact of congenital uterine anomalies on reproductive outcomes of IVF/ICSI-embryo transfer: a retrospective study.

OBJECTIVE: To study the impact of congenital uterine anomalies on reproductive outcomes after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)-embryo transfer (ET). METHODS: A retrospective study including a total of 865women with congenital uterine anomalies and 865 age and admission time matched controls who underwent the first IVF/ICSI-ET cycle between January 2010 and December 2019 was conducted. Women with uterine anomalies were classified into canalization defect (complete septate uterus and subseptate uterus) and unification defect (unicornuate uterus, bicornuate uterus, and didelphus uterus) according to the processes of abnormal embryological development. Control women were selected by age (± 1.0 year) and admission time (± 6 months) matched with a 1:1 ratio. The reproductive outcomes were compared between women with uterine anomalies and the controls. The primary outcome was live birth; secondary outcomes were clinical pregnancy, ectopic pregnancy, preterm delivery, and spontaneous pregnancy loss. RESULTS: Compared with women with a normal uterus, women with canalization defects were less likely to experience live birth [84/332 (25.3%) vs 128/332 (38.6%), RR: 0.647, 95% CI 0.513-0.815, P < 0.001]. They also had a lower clinical pregnancy rate [126/332 (38.0%) vs 206/332 (62.0%), RR: 0.829, 95% CI 0.690-0.997, P = 0.046] and experienced a higher first-trimester pregnancy loss rate [25/126 (19.8%) vs 11/206 (5.3%), RR: 2.716, 95% CI 1.393-5.295, P = 0.003]. Compared with women with a normal uterus, women with a unification defect were also less likely to experience live birth [132/533 (24.8%) vs 219/533 (41.1%), RR: 0.713, 95% CI 0.586-0.868, P = 0.001]. Women with a unification defect had lower clinical pregnancy rates [182/533 (34.1%) vs 263/533 (49.1%), RR: 0.813, 95% CI 0.695-0.952, P = 0.010] and increased first-trimester pregnancy loss [36/182 (19.8%) vs 20/263 (7.6%), RR: 3.288, 95% CI 1.776-6.085, P < 0.001]. While uterine anomaly seemed not increase the risk of preterm birth, ectopic pregnancy and second-trimester pregnancy loss. CONCLUSIONS: Both canalization defects and unification defects were associated with lower fertility outcomes, including lower live birth rates, lower clinical pregnancy rates, and higher early miscarriage rates.